Sheng M, Liao Y J, Jan Y N, Jan L Y
Department of Physiology, Howard Hughes Medical Institute, University of California, San Francisco 94143-0724.
Nature. 1993 Sep 2;365(6441):72-5. doi: 10.1038/365072a0.
A wide variety of voltage-gated K+ channels are involved in the regulation of neuronal excitability and synaptic transmission. Their heterogeneity arises in part from the large number of genes encoding different K+ channel subunits (reviewed in ref. 1). In addition, heterologous expression studies indicate that assembly of distinct subunits into heteromultimeric channels may contribute further to K+ channel diversity. A question has been whether heteromeric K+ channels actually form in vivo, and if so, whether specific combinations of subunits could account for major K+ currents identified in neurons. We present here biochemical evidence that Kv1.4 and Kv1.2, two K+ channel subunits of the Shaker subfamily, co-assemble in rat brain. The Kv1.4/Kv1.2 heteromultimer combines features of both parent subunits, resulting in an A-type K+ channel. Immunocytochemical evidence suggests that the heteromultimers are localized in axons and nerve terminals. We propose that Kv1.4/Kv1.2 heteromultimers may form the molecular basis of a presynaptic A-type K+ channel involved in the regulation of neurotransmitter release.
多种电压门控钾通道参与神经元兴奋性和突触传递的调节。它们的异质性部分源于编码不同钾通道亚基的大量基因（参考文献1中有综述）。此外，异源表达研究表明，不同亚基组装成异源多聚体通道可能进一步增加钾通道的多样性。一个问题是异源多聚体钾通道在体内是否真的形成，如果是，亚基的特定组合是否可以解释在神经元中鉴定出的主要钾电流。我们在此提供生化证据表明，Shaker亚家族的两个钾通道亚基Kv1.4和Kv1.2在大鼠脑中共同组装。Kv1.4/Kv1.2异源多聚体结合了两个亲本亚基的特征，形成了一种A型钾通道。免疫细胞化学证据表明，异源多聚体定位于轴突和神经末梢。我们提出，Kv1.4/Kv1.2异源多聚体可能构成参与神经递质释放调节的突触前A型钾通道的分子基础。
